Cholecystokinin and gastrin as immune modulating hormones: Implications and applications.

Cholecystokinin (CCK) and gastrin are gastrointestinal hormones traditionally recognised for their roles in digestion. However, it has been recognised that these hormones may also modulate immune function. Here, we examine the immune-modulating effects of CCK and gastrin, and explore the functional significance of this dual role.

GLP-1R agonist therapy and vaccine response: Neglected implications.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide (Ozempic®), have emerged as effective treatments for diabetes and weight management. However, recent evidence indicates that GLP-1R signalling influences various tissues, including the immune system. Notably, GLP-1 has a short half-life (< 5 minutes) and exists in the picomolar range, while GLP-1RAs like semaglutide have extended half-lives of several days and are administered at supraphysiological doses.

Insulin-mediated immune dysfunction in the development of preeclampsia.

Epidemiological observations implicate insulin resistance as a predisposing factor in the development of preeclampsia (PE). It is also well established that PE manifests in the context of a dysregulated immune response at the maternal-foetal interface, though all the underlying drivers of such immune dysregulation remains to be accounted for. Although it has long been known that various immune cells express insulin receptors following immune activation, it is only recently that insulin signalling has been shown to play a key role in immune cell differentiation, survival and effector function through its canonical activation of the PI3K/Akt/mTOR pathway.

The onco-immunological implications of Fusobacterium nucleatum in breast cancer.

Breast cancer is a leading cause of death worldwide and a better understanding of this disease is needed to improve treatment outcomes. Recent evidence indicates that bacterial dysbiosis is associated with breast cancer, but the bacteria involved remain poorly characterised. Furthermore, an association between periodontal disease, characterised by oral dysbiosis, and breast cancer have also been discovered, but the mechanisms responsible for this association remains to be elucidated.

The immuno-oncological implications of insulin.

Emerging evidence has implicated insulin in regulating the phenotypes of various immune cells through canonical downstream signalling effectors of insulin, namely, the PI3K/Akt/mTOR pathway. Notably, these signalling components also exhibit crosstalk with other immune signalling pathways, such as the JAK/STAT pathway (activated by cytokines and growth factors), and, importantly, are also negatively regulated by the immune checkpoint blockers (ICBs), PD-1 and CTLA-4. Here, we point out recent findings, suggesting that insulin may promote a pro-inflammatory phenotype with potential implications on ICB therapy.

Nutritional support in sepsis: when less may be more.

Despite sound basis to suspect that aggressive and early administration of nutritional support may hold therapeutic benefits during sepsis, recommendations for nutritional support have been somewhat underwhelming. Current guidelines (ESPEN and ASPEN) recognise a lack of clear evidence demonstrating the beneficial effect of nutritional support during sepsis, raising the question: why, given the perceived low efficacy of nutritionals support, are there no high-quality clinical trials on the efficacy of permissive underfeeding in sepsis? Here, we review clinically relevant beneficial effects of permissive underfeeding, motivating the urgent need to investigate the clinical benefits of delaying nutritional support during sepsis.

Insulin as an immunomodulatory hormone.

Insulin plays an indispensable role in the management of hyperglycaemia that arises in a variety of settings, including Type I and II diabetes, gestational diabetes, as well as is in hyperglycaemia following a severe inflammatory insult. However, insulin receptors are also expressed on a range of cells that are not canonically implicated in glucose homeostasis. This includes immune cells, where the anti-inflammatory effects of insulin have been repeatedly reported.

Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model.

Background: Doxorubicin is currently the most effective chemotherapeutic drug used to treat breast cancer. It has, however, been shown that doxorubicin can induce drug resistance resulting in poor patient prognosis and survival. Studies reported that the interaction between signalling pathways can promote drug resistance through the induction of proliferation, cell cycle progression and prevention of apoptosis.

How Does Inflammation-Induced Hyperglycemia Cause Mitochondrial Dysfunction in Immune Cells?

Inflammatory mediators have an established role in inducing insulin resistance and promoting hyperglycemia. In turn, hyperglycemia has been argued to drive immune cell dysfunction as a result of mitochondrial dysfunction. Here, the authors review the evidence challenging this view.

The role of bile acids in nutritional support.

Nutritional support continues to receive much attention as a possible intervention to prevent loss of lean tissue mass, promote recovery and re-establish proper immune function in critical care patients. Yet there remains much controversy regarding the clinical efficacy of such interventions. In addition to the direct effect of nutrition in terms of micro- and macronutrient content, nutritional formulations may exert an effect via the physiological response to feeding.

Inflammation-induced metabolic derangements or adaptation: An immunometabolic perspective.

Inflammatory mediators have a well-established role in mediating metabolic disturbances. Chronic low-grade inflammation is implicated in the pathogenesis of obesity and the development of metabolic syndrome. This phenomenon is even more pronounced in severe inflammatory states such as in critically ill patients where hyperglycaemia invariably manifests.

Role of PKM2 in directing the metabolic fate of glucose in cancer: a potential therapeutic target.

Background: Many of the hallmarks of cancer are not inherently unique to cancer, but rather represent a re-enactment of normal host responses and activities. A vivid example is aerobic glycolysis ('Warburg effect'), which is used not only by cancer cells but also by normal cells that undergo rapid proliferation. A common feature of this metabolic adaptation is a shift in the expression of pyruvate kinase (PK) isoform M1 to isoform M2.

Bone resorption: supporting immunometabolism.

Activation of the immune system is associated with an increase in the breakdown of various peripheral tissues, including bone. Despite the widely appreciated role of inflammatory mediators in promoting bone resorption, the functional value behind this process is not completely understood. Recent advances in the field of immunometabolism have highlighted the metabolic reprogramming that takes place in activated immune cells.

Doxorubicin resistance in breast cancer: A novel role for the human protein AHNAK.

Understanding the response of cancer cells to anti-cancer therapies is crucial to unraveling and preventing the development of therapeutic resistance. The human AHNAK protein is a giant scaffold protein implicated in several diverse cellular functions. The role of AHNAK in cancer is however unclear as the protein has previously been described as a tumor suppressor, as well as being essential for tumor metastasis and invasion, while also being implicated in selected chemotherapeutic responses.

Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity.

Over-nutrition and a sedentary lifestyle are the driving forces behind the development of metabolic diseases. Conversely, caloric restriction and exercise have proven to be the most effective strategies in combating metabolic diseases. Interestingly, exercise and caloric restriction share a common feature: both represent a potent mechanism for upregulating autophagy.

Domesticating Cancer: An Evolutionary Strategy in the War on Cancer.

Since cancer shares the same molecular machinery as the host, most therapeutic interventions that aim to target cancer would inadvertently also adversely affect the host. In addition, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving.

Hyperglycaemia in critically ill patients: the immune system's sweet tooth.

There is an ongoing debate regarding the efficacy of glycaemic control in critically ill patients. Here we briefly highlight the key function of elevated glucose in critically ill patients, namely, to enable elevation of aerobic glycolysis in rapidly dividing cells. In particular, aerobic glycolysis provides metabolic intermediates necessary for expansion of biomass in immune cells and promotion of tissue repair.

Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection.

Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy.

Cancer stem cells: A product of clonal evolution?

The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells.

Sickness-Associated Anorexia: Mother Nature's Idea of Immunonutrition?

During an infection, expansion of immune cells, assembly of antibodies, and the induction of a febrile response collectively place continual metabolic strain on the host. These considerations also provide a rationale for nutritional support in critically ill patients. Yet, results from clinical and preclinical studies indicate that aggressive nutritional support does not always benefit patients and may occasionally be detrimental.

Autophagy--A free meal in sickness-associated anorexia.

Activation of the immune system is metabolically costly, yet a hallmark of an infection is a reduction in appetite with a subsequent reduction in metabolite provision. What is the functional value of decreasing nutrient intake when an infection imposes large demands on metabolic parameters? Here, we propose that sickness-associated anorexia (SAA) upregulates the ancient process of autophagy systemically, thereby profoundly controlling not only immune- but also nonimmune-competent cells. This allows an advanced impact on the resolution of an infection through direct pathogen killing, enhancement of epitope presentation and the contribution toward the clearance of noxious factors.

Cancer tolerance, resistance, pathogenicity and virulence: deconstructing the disease state.

Immunologists have recently taken note of the fact that a host not only resists infection, but also exhibits a capacity to manage the pathology associated with such infection - a concept referred to as tolerance. Here we explore how the tolerance/resistance (T/R) framework can be implemented within an oncological context and explore a number of implications. In particular, the T/R framework distinguishes between pathology manifesting from extensive tumor burden, versus cancers intrinsically expressing a more pathogenic phenotype.